title: Genetic polymorphism of CCR5 gene and HIV disease: the heterozygous (CCR5/delta ccr5) genotype is neither essential nor sufficient for protection against disease progression. Swiss HIV Cohort.
abstract: Homozygous (delta ccr5/delta ccr5) and heterozygous (CCR5/delta ccr5) deletions in the beta-chemokine receptor 5 (CCR5) gene, which encodes for the major co-receptor for macrophage-tropic HIV-1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/delta ccr5 genotype was found more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p < 0.0001), in agreement with previous studies. Kaplan-Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4+ T cell counts > 500/microl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/delta ccr5 genotype. However, when LTNP were analyzed separately, no significant differences in CD4+ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild-type (69% of LTNP) and the heterozygous (31.0%) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/delta ccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/delta ccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.
authors.affiliation: Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: R A
authors.initials: RA
authors.lastname: Morawetz
authors.forename: G P
authors.initials: GP
authors.lastname: Rizzardi
authors.forename: D
authors.initials: D
authors.lastname: Glauser
authors.forename: O
authors.initials: O
authors.lastname: Rutschmann
authors.forename: B
authors.initials: B
authors.lastname: Hirschel
authors.forename: L
authors.initials: L
authors.lastname: Perrin
authors.forename: M
authors.initials: M
authors.lastname: Opravil
authors.forename: M
authors.initials: M
authors.lastname: Flepp
authors.forename: J
authors.initials: J
authors.lastname: von Overbeck
authors.forename: M P
authors.initials: MP
authors.lastname: Glauser
authors.forename: S
authors.initials: S
authors.lastname: Ghezzi
authors.forename: E
authors.initials: E
authors.lastname: Vicenzi
authors.forename: G
authors.initials: G
authors.lastname: Poli
authors.forename: A
authors.initials: A
authors.lastname: Lazzarin
authors.forename: G
authors.initials: G
authors.lastname: Pantaleo
mesh_terms: D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D015497:HIV-1; D006579:Heterozygote; D006801:Humans; D011110:Polymorphism, Genetic; D011379:Prognosis; D019713:Receptors, CCR5 / Q000235:genetics* / Q000276:immunology
chemical_list: D019713:Receptors, CCR5